Agrawal Samir, Vamadevan Padman, Mazibuko Ndaba, Bannister Robin, Swery Raphael, Wilson Shanna, Edwards Sarah
Blizard Institute, Queen Mary University of London, London, United Kingdom.
St Bartholomew's Hospital, Bart's Health NHS Trust, London, United Kingdom.
Front Pharmacol. 2019 Jun 27;10:681. doi: 10.3389/fphar.2019.00681. eCollection 2019.
In oncology, preclinical and early clinical data increasingly support the use of a number of candidate "non-cancer" drugs in an off-label setting against multiple tumor types. In particular, metabolically targeted drugs show promise as adjuvant chemo and radiosensitizers, improving or restoring sensitivity to standard therapies. The time has come for large scale clinical studies of off-label drugs in this context. However, it is well recognized that high-cost randomized controlled trials may not be an economically viable option for studying patent-expired off-label drugs. In some cases, randomized trials could also be considered as ethically controversial. This perspective article presents a novel approach to generating additional clinical data of sufficient quality to support changes in clinical practice and relabeling of such drugs for use in oncology. Here, we suggest that a pluralistic evidence base and triangulation of evidence can support clinical trial data for off-label drug use in oncology. An example of an off-label drug protocol brought to the clinic for glioblastoma patients is presented, along with preliminary retrospective data from the METRICS study (NCT02201381). METRICS is a novel participant-funded, open-label, non-randomized, single-arm real-world study designed to gather high-quality evidence on the safety, tolerability, and effectiveness of four off-label metabolically targeted medicines as an adjunctive cancer treatment for glioblastoma patients.
在肿瘤学领域，临床前和早期临床数据越来越多地支持在多种肿瘤类型的非标签用药中使用一些候选“非癌症”药物。特别是，代谢靶向药物有望作为辅助化疗和放疗增敏剂，提高或恢复对标准疗法的敏感性。开展此类非标签药物大规模临床研究的时机已经成熟。然而，众所周知，对于研究专利过期的非标签药物而言，高成本的随机对照试验可能在经济上不可行。在某些情况下，随机试验在伦理上也可能存在争议。这篇观点文章提出了一种新方法，用于生成足够高质量的额外临床数据，以支持临床实践的改变以及此类药物在肿瘤学中重新标注用途。在此，我们建议多元证据基础和证据三角法能够为肿瘤学中非标签药物使用的临床试验数据提供支持。文中展示了一个针对胶质母细胞瘤患者应用于临床的非标签药物方案示例，以及METRICS研究（NCT02201381）的初步回顾性数据。METRICS是一项新型的由参与者资助的、开放标签、非随机、单臂的真实世界研究，旨在收集关于四种非标签代谢靶向药物作为胶质母细胞瘤患者辅助癌症治疗的安全性、耐受性和有效性的高质量证据。
